Monthly Update
Issue Contributors: Kimberly Bebar, DVM and Virginia Sinnott, DVM, DACVECC
Editor:
William B Henry DVM, DACVS  
August 2012

Anticoagulant Rodenticide Toxicity

Kimberly Bebar, DVM and Virginia Sinnott, DVM, DACVECC

CCVS Emergency and Critical Care Resident




Ingestion of anitcoagulant rodenticides (ACRs) is one of the most common toxicities seen in veterinary medicine. The ACRs include those listed in table 1 below. It is important to note that not all rodenticides ingested are anticoagulant. Bromethalin, cholecalciferol, strychnine, and zinc phosphide are common rodenticides that do not work by altering the coagulation cascade and affecting hemostasis. As such, it is important to identify the active ingredient (not just the brand name) before assuming a rat poison's mechanism of action is anticoagulant in origin.

 



As Table 1 illustrates, there are numerous possible active ingredients in ACRs and thus it has been our experience at CCVS that in most cases of toxicity or ingestion, the actual amount ingested can be difficult to determine. Therefore, all ingestions are treated as though they are potentially toxic.

 

Mechanism of action

Anticoagulants are ingested and transported to the liver via chylomicrons and the portal vein. In the liver, Vitamin K1 is required for the production of functional clotting factors II, VII, IX, and X. Vitamin K1 hyrodquinone is converted to vitamin Vitamin K1 epoxide in the formation of these clotting factors. The Vitamin K1 epoxide is recycled back into Vitamin K1 hydroquinone by the enzyme Vitamin K1 epoxide reductase. It is this recycling enzyme that is inhibited by anticoagulant rodenticides. Thus ingestion of these toxins increases the body's requirement for vitamin K far beyond what can be ingested in the diet, leading to a relative shortage of vitamin K and the production of dysfunctional clotting factors II, VII, IX, and X.1

 

 

There are two distinct populations of pets presenting for rodenticide exposure, acute ingestion and symptomatic toxicity. We will discuss these individually as treatment is very different for these two populations.

 

Acute Ingestion

Pets presented for ingestion within the last several hours are classified as acute ingestion. They have no clinical signs of rodenticide toxicity but are suspected or known to have ingested the drug. The focus on treatment for pets with acute ingestion is decontamination. Emesis can be induced with apomorphine (0.03mg/kg IV, IM, or subconjuctival) or hydrogen peroxide (5mL/5 lbs by mouth, not to exceed 45mL per dog). Apomorphine is preferred as hydrogen peroxide may predispose to esophagitis. Activated charcoal with or without sorbitol (10mL/kg) can be given to prevent any further absorption in the gastrointestinal tract. Generally at CCVS we administer activated charcoal without sorbitol when treating patients as outpatients to prevent dehydration and hyperosmolality that can occur with activated charcoal use.

 

Traditionally, these patients are then treated with vitamin K1 (2.5 - 5mg/kg PO divided into twice daily doses). However, vitamin K1 has been reported to cause hemolysis in some patients and is not a benign medication. Although it may still be required in some cases, a recently published study indicates that we may not need to give vitamin K1 following acute ingestion. In this study, 115 dogs that had ingested rodenticide within 6 hours of presentation to the hospital were treated with decontamination and then rechecked in 2-6 days. A prothrombin time (PT) was checked on these dogs. Only 8.3% of them had a prolonged PT and were started on vitamin K1 at that time. No patients had any evidence of hemorrhage.2

 

If the decontamination efforts are successful, an alternative to administering pills for several weeks is to recheck a PT 48 hours after ingestion. The PT will prolong prior the onset of clinical bleeding and the activated partial thromboplastin time (aPTT) as factor VII has the shortest plasma half-life. If it is prolonged, vitamin K1 can be started at that time if the clinician knows exposure was indeed above toxic levels. If the PT is normal at the 48 hour recheck, no further therapy or rechecks are required. At CCVS, we employ this method along with a stern warning that failure to return for the recheck PT could result in death of the pet if bleeding occurs. We also perform the PT testing in-house to avoid delays that could lead to bleeding while awaiting results.

 

Clinical Toxicity

This patient population ingested an ACR some days prior to the onset of clinical signs unbeknownst to the owner. The diagnosis is made less on identifying what toxin was eaten than by confirming a coagulopathy in the face of active bleeding. Clincial signs of toxicity usually occur within 3-5 days of ingestion. They may include hematuria, hematemesis, epistaxis, hematomas, coughing, respiratory distress, or lethargy and depression. Hemorrhage can occur at any mucosal site or in the thoracic or abdominal cavities. A retrospective study reported that signs of internal hemorrhage are seen more commonly than external hemorrhage.3

 

Diagnosis is traditionally made by evaluation of the platelet count and clotting times. In a patient with evidence of hemorrhage, the platelet count may be decreased, but should not be below 50,000/mL. Spontaneous hemorrhage is not seen from thrombocytopenia until the count is less than 50,000/mL. The PT and aPTT will both be prolonged. Classically, the PT is more prolonged as factor VII has the shortest plasma half-life. In active hemorrhage, both the PT and aPTT may be significantly prolonged (often above the detectable range).

 

There are numerous reasons for patients to have mild thrombocytopenia and elevated PT and aPTT resulting in clinical hemorrhage including disseminated intravascular coagulation and hereditary coagulopathies. To confirm diagnosis of rodenticide toxicity, a rodenticide panel is available through the University of Pennsylvania Toxicology Laboratory as well as UC Davis+ Panels such as this can be helpful in confirming diagnosis of rodenticide toxicity, but will take several days for results to be available.

 

Treatment involves stabilizing the patient and supplying them with functional clotting factors. This is typically done with blood product transfusions. Fresh whole blood (20mL/kg) can be used to supply both red blood cells and clotting factors. Fresh frozen or frozen plasma (10mL/kg) can be used to supply clotting factors. Because a unit of Fresh frozen plasma becomes "frozen plasma" after a year, and frozen plasma is viable for another 2 years, plasma useful for anticoagulant rodenticide intoxication has shelf life of up to 3 years if stored frozen. This means plasma can be kept in stock at any veterinary hospital that will likely treat one bleeding anticoagulant rodenticide case in that time-frame. The patient should be transfused until the PT and aPTT are within normal limits and active hemorrhage has subsided. This means that patients may require multiple transfusions, typically at CCVS dogs require 10-20mL/kg of plasma to normalize the PT and aPTT but there have been cases that have required much more as well as red blood cells due to active bleeding and consumption of clotting factors. 

Treatment specific to the bleeding organ may be required. Oxygen therapy is provided to animals with hemorrhage into the cervical tissues, mediastinum, pleural space, or lung parenchyma. Removal of blood in body cavities must be considered carefully. Thoraco- or abdominocentesis is generally avoided until plasma is given unless the patient is in danger of ventilatory failure. Intracranial hemorrhage leading to signs of intracranial hypertension can be treated with hypertonic saline (7-7.5% NaCl 4mL/kg IV over 30 minutes). Administration of mannitol is controversial as mannitol may leak into the area of hemorrhage and act to recruit additional fluid, worsening signs of intracranial hypertension.

 

Vitamin K1 therapy will be required in these patients for up to 30 days, but should not be used as the sole therapy because it takes 12-24 hours from the time of administration for the liver to produce functional clotting factors. In a patient with active hemorrhage, this will lead to prolonged bleeding for that length of time which could be life-threatening. With aggressive treatment, often employing the use of blood products, rodenticide toxicity usually carries a good prognosis. Although the hemorrhaging organ can affect prognosis with bleeding in the lungs and brain giving the clinician less time to control hemorrhage, a recent study showed overall survival to be 90% with 79% of patients discharged from the hospital within 48 hours.3

 

References

1 Murphy, MJ. Rodenticides. Vet Clin Small An 32 (2002): 469-484.

2 Pachtinger, GE, Otto, CM, Syring RS. Incidence of prolonged prothrombin time in dogs following gastrointestinal decontamination for acute anticoagulant rodenticide ingestion. JVECC. 2008. Vol 18 (3): 285-291.

3 Haines B. Anticoagulant rodenticide ingestion and toxicity: a retrospective study of 252 canine cases. Aust Vet Pract. June 2008; 38(2): 38-50.

 

Footnotes

+ http://www.vet.upenn.edu/FacultyandDepartments/Pathobiology/PathologyandToxicology/tabid/412/Default.aspx 

Injection Site Sarcomas

New England Veterinary Oncology Group

Michelle Silver, DVM, DACVIM (oncology), Andy Abbo DVM, MS, DACVIM (oncology)  

 

Tumors associated with previous injections have been collectively termed "injection site sarcomas" due to their anatomic location at common sites of SQ injections. The overall prevalence of these tumors in the cat is unknown, but there are various sources reporting rates of one case per 10,000 up to 10 per 10,000 cats, and most commonly after a rabies or leukemia virus vaccination. This means between 2,200 to 22,000 cases of sarcomas are diagnosed each year. These tumors are most commonly fibrosarcomas, but osteosarcoma, histiocytic sarcoma, and other sarcomas have also been described. These are locally invasive tumors, with around a 20-30% chance of metastasis. The most common site for metastasis is the lungs.

 

The precise pathogenesis of an injection site sarcoma is unknown, but may involve the stimulation of these cells by highly immunogenic and persistent adjuvants or other vaccine components that result in inflammation, which alone or in association with unidentified carcinogens or oncogenes leads to neoplastic transformation and tumor development. Studies have found that approximately 75% of injection sarcomas contain the p53 oncogene. P53 is a gene that mediates normal programmed cell death. Mutations in the p53 gene will result in unrestricted cell growth and survival of the tumor cells. Platelet derived growth factor (PDGF) has also been shown to play a part in the development of injection site sarcomas. PDGF is normally released by disintegrating platelets and stimulates the division of fibroblasts as part of normal wound healing. Fibroblasts respond to PDGF, but do not produce it. When PDGF is inappropriately present, normal fibroblasts can be transformed into sarcoma cells.

 

Histopathology is usually characterized by marked nuclear and cellular pleomorphism, high mitotic activity, and large central zones of necrosis; all features are consistent with aggressive biologic behavior. There is often the presence of a peripheral inflammatory infiltrate consisting of lymphocytes and macrophages. Macrophages often contain bluish-grey foreign material.

 

Differentiating between benign post vaccination injection site granulomas and an injection site sarcoma is important and it is recommended to manage a mass that develops at a previous injection site as if it were malignant until proven otherwise. A lesion at a previous injection site should be fully assessed and aggressively managed if it meets any one of the following criteria:

    • Persists more than 3 months
    • Is larger than 2cm in diameter
    • Increases in size one month after injection.

 Staging is recommended prior to any definitive therapy and includes: thoracic imaging (radiographs vs CT), regional lymph node palpation/aspiration, bloodwork , and +/- an abdominal ultrasound. A fine needle aspirate or an incisional biopsy is recommended before surgical excision to try and obtain a definitive diagnosis; however, histopathology is often necessary as cytology may be inconclusive. Care should be taken to assure that the biopsy tract is in the area to be surgically resected. A CT scan or MRI is recommended to assess the extent of the tumor and to ensure it is amendable to surgical excision.

 

*CT scan of patient with a fibrosarcoma along the left thigh indicated by the white arrow

 

Surgery is the treatment of choice and the first surgery is the best chance for long term local control. Cats that undergo several surgeries have been found to have a decreased overall survival time. Cats who undergo radical surgery have a median time to first recurrence of 350 days vs 79 days for cats with a marginal resection. Unfortunately, complete resection is achieved in <50% of cats, and with surgery alone, 35% of cats will be disease free at 1 year. It has been recommended to vaccinate low on the limb so that an amputation can be considered as a curative intent surgery. When tumors arise in the interscapular region or the flank, surgical excision is much more extensive and usually requires body wall resection, partial scapulectomy or removal of the dorsal spinous process.  

Due to the difficulty with obtaining wide margins, adjuvant radiation therapy is recommended for narrow or incompletely excised tumors. Definitive radiation therapy consists of 15-17 treatments given Monday-Friday for 3-3.5 weeks at our Waltham facility. Mild to moderate acute local side effects can include erythema, alopecia, and dry desquamation of the skin. Fortunately, these side effects are transient and usually are starting to heal nicely 1-2 weeks after the radiation is complete with minimal supportive care needed. Studies have not found any difference in local control rates when you compare giving radiation pre-operatively vs post surgery. When radiation therapy is combined with surgery, the median survival time is 600-842 days with 85% of cats alive at 1 year. Unfortunately, 28-45% of tumors can still recur despite this multi-modality treatment. If the tumors are deemed non-resectable then palliative radiation may be considered. Palliative radiation therapy consists of three treatments administered at weekly intervals, though the benefit of this type of radiation therapy has not been well evaluated for local tumor control it is very well tolerated with limited to no side effects noted and in addition it is especially useful for pain control where ~70% experience pain relief for an average of 3-4 months.

 

The benefit of chemotherapy remains unclear at this time and its use is mostly anecdotal as it has not been shown to improve the overall survival time though may help to extend time to local tumor recurrence. Due to the aggressive nature of these tumors chemotherapy may be warranted for some patients with the most commonly used agent being adriamycin. Fortunately, chemotherapy is very well tolerated in cats with less than 5% experiencing significant adverse effects. Side effects can include vomiting, diarrhea, anorexia, bone marrow suppression, and renal toxicity.

 

When addressed early and aggressively, cats can have a good prognosis.

In This Issue
Anticoagulant Rodenticide Toxicity
NEVOG News: Injection Site Sarcomas
CT Corner
Abstract
Continuing Education
Tech Tip
Newsletter Archive
CT Corner 


Our CT Corner this month this month highlights the importance of pre-operative planing when dealing with vaccine induced fibrosarcomas in cats. The CT confirms the need for wide excision of these tumors, i.e. at least 2-3 cm of tissue on ALL peripheral tumor borders. In this case the dorsal spinous processes would need to be included in the tumor resection. This can be done without significantly changing the cat's appearance (surgeons do it all the time in the dog when doing dorsal decompressive laminectomies, often over many vertebrae). A recent paper shows complete excision in 97% of cases and 14% local recurrence after excision with 5 cm. peripheral margins and two fascial planes or bone deep. (See ABSTRACT Phelps et al JAVMA 2011; 239: 97-106).

 

VIDEO:  

Micho Seal Point Siamese Sarcoma

 

ABSTRACT
Radical excision with five-centimeter margins for treatment of feline injection-site sarcomas: 91 cases (1998-2002) Holly A. Phelps, DVM et al JAVMA 2011 239: 97-106

Objective - To evaluate outcomes of radical excision of feline injection-site sarcomas (ISS) via assessment of local recurrence and metastasis rates, survival times, and complications associated with surgery.

Design-Retrospective case series.

 

Animals - 91 cats with ISS.

 

Procedures - Medical records of cats that had radical excision of ISS without adjunctive treatment were reviewed. Information extracted included sex, type of surgical procedure, histologic tumor grade, tumor diameter, time from tumor detection to definitive surgery, complications associated with surgery, whether tumors recurred locally or metastasized, and survival times. Diagnosis of ISS was histologically confirmed, and additional follow-up was performed.

 

Results - Overall median survival time was 901 days. Thirteen of 91 (14%) cats had local tumor recurrence; 18 (20%) cats had evidence of metastasis after surgery. Median survival time of cats with and without recurrence was 499 and 1,461 days, respectively. Median survival time of cats with and without metastasis was 388 and 1,528 days, respectively. Tumor recurrence and metastasis were significantly associated with survival time, whereas other examined variables were not. Major complications occurred in 10 cats, including 7 with incisional dehiscence.

 

Conclusions and Clinical Relevance - Radical excision of ISS resulted in a metastasis rate similar to rates reported previously; the local recurrence rate appeared to be substantially less than rates reported after less aggressive surgeries, with or without adjuvant treatment. Major complication rates were similar to rates reported previously after aggressive surgical resection of ISS. Radical excision may be a valuable means of attaining an improved outcome in the treatment of feline ISS.

 

Continuing Education Opportunies

The fall/winter lecture topics will be listed in the upcoming  September issue.   

  

Tech Tip
Our TechTip this month is the economics of using pre packaged surgery packs that contain disposable impervious paper drapes, electric cautery, light condoms, surgical blades etc. ( see list below ). Cardinal Health customizes these packs for our two referral practices BVS and CCVS. They contain different material and have different cost (BVS $11.00 and CCVS $17.00). When we cost accounted the technicians time to launder cloth drapes, dry, wrap, sterilize them along with packaging and sterilizing other included items like light handle covers it was much more economical to use these pre packaged sterile surgery packs. The contact information and cost is included to help in your decision process.

Anthony Piscitelli  

Presource Convertors Specialist

Metro New York & New England

Cardinal Health

cell:  (203) 828-7368 

fax:  (614) 553-9760 

 

Surgical Packs and Non-sterile Kits ... custom and standard     

Diagnostic Procedure Trays

Pain Management Kits

Convertors.

 

Boston Veterinary Specialists Basic Pack     

 

We charge the client for them along with our other medical supplies for a surgical procedure (click here to see example).      

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